Transferrin-mediated fullerenes nanoparticles as Fe2+-dependent drug vehicles for synergistic anti-tumor efficacy.
【作者】Huijuan Zhang, Lin Hou, Xiaojing Jiao, Yandan Ji, Xiali Zhu, Zhenzhong Zhang
【期刊名】 Biomaterials
【影响因子】 2015年: 8.387
【作者单位】 School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, PR China
【年，卷(期)：页码】2015, 37: 353-366
【关键词】Iron-dependent artesunate, Transferrin, Hyaluronic acid-derivatized fullerenes vehicles, Photodynamic therapy
【摘要】Artesunate (AS) is an iron-dependent drug, which has been used extensively as anti-malarial drugs worldwide with no obvious side effects. Recently, studies have shown that AS also possess profound cytotoxicity against tumor cells. However, simultaneous delivery of hydrophobic AS and Fe2+ into tumor cells remains a major challenge. Herein, we report a new kind of active-targeting preparations which could not only specially target to tumor cells but also synchronously transfer AS and irons into tumor tissue. In this study, hyaluronic acid (HA) was grafted onto fullerene to get a water-soluble biomaterial (HA-C60) with excellent biocompatibility, and then combined with transferrin (Tf) to obtain a multifunctional drug delivery system (HA-C60-Tf) with significant tumor-targeting efficacy and powerful photodynamic therapy capacity. Finally, AS was adsorbed on HA-C60-Tf with a high loading efficacy of 162.4% (weight ratio of AS: HA-C60-Tf). Compared with free AS, remarkably enhanced antitumor efficacy of AS-loaded HA-C60-Tf nanoparticles was realized both in a cultured MCF-7 cells in vitro and in a tumorbearing murine model in vivo, due to increased intracellular accumulation of AS in tumor and activated mechanism by co-delivery of Tf and AS analogs. Furthermore, with laser irradiation in vivo, the relative tumor volume (V/V0) of HA-C60-Tf/AS declined by half, from 1.72 ± 0.12 to 0.84 ± 0.07, suggesting a new way with multi-mechanism for tumor treatment was developed.
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